3-Pyridinecarboxaldehyde → 2-(Pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-one

HRID 45284

Reaction equation

HRID 45284 reaction equation
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=[O:10])[CH2:3]2.[OH-].[K+].[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=O)[CH:14]=1>CO>[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=[C:3]2[C:4](=[O:10])[CH:5]3[CH2:8][CH2:9][N:2]2[CH2:7][CH2:6]3)[CH:14]=1

Participants

5

Reactant 3

HCID 103713-PyridinecarboxaldehydeHCID 14797Potassium HydroxideHCID 1020191-Azabicyclo(2.2.2)octan-3-one, hydrochloride (1:1)

Product 1

HCID 6118222-(Pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-oneYield 89.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-Quinuclidinone hydrochloride (8.25 kg, 51.0 mol) and methanol (49.5 L) were added to a 100 L glass reaction flask, under an nitrogen atmosphere, equipped with a mechanical stirrer, temperature probe, and condenser. Potassium hydroxide (5.55 kg, 99.0 mol) was added via a powder funnel over an approximately 30 min period, resulting in a rise in reaction temperature from 50° C. to 56° C. Over an approximately 2 h period, 3-pyridinecarboxaldehyde (4.80 kg, 44.9 mol) was added to the reaction mixture. The resulting mixture was stirred at 20° C.±5° C. for a minimum of 12 h, as the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was filtered through a sintered glass funnel and the filter cake was washed with methanol (74.2 L). The filtrate was concentrated, transferred to a reaction flask, and water (66.0 L) was added. The suspension was stirred for a minimum of 30 min, filtered, and the filter cake was washed with water (90.0 L) until the pH of the rinse was 7-9. The solid was dried under vacuum at 50° C.±5° C. for a minimum of 12 h to give 8.58 kg (89.3%) of 2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octan-3-one.

Workup

  1. customequipped with a mechanical stirrer
  2. customresulting in a rise in reaction temperature from 50° C. to 56° C
  3. customUpon completion of the reaction
  4. filtrationthe reaction mixture was filtered through a sintered glass funnel
  5. washthe filter cake was washed with methanol (74.2 L)
  6. concentrationThe filtrate was concentrated
  7. customtransferred to a reaction flask
  8. additionwater (66.0 L) was added
  9. stirringThe suspension was stirred for a minimum of 30 min
  10. filtrationfiltered
  11. washthe filter cake was washed with water (90.0 L) until the pH of the rinse
  12. customThe solid was dried under vacuum at 50° C.±5° C. for a minimum of 12 h

Sources & evidence

ORD record
ord-cd5c7f120af947d0aff7634e24a6554d
Source dataset
uspto-grants-2013_09
Patent number
US08541446B2

Linked notes

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